The function of the lungs is to maintain normal arterial oxygen, arterial carbon dioxide and arterial pH. Pulmonary function tests are used to measure lung volumes, airflow resistance patterns and efficiency of gaseous exchange.

Three main approaches can be used in the compliant older child:
Spirometry is the mainstay of most paediatric lung function protocols and is used to measure dynamic lung volumes and flow rates during forced ventilatory manoeuvres.
Plethysmography is used to measure static lung volumes, in particular total lung capacity and residual volume. Effort independent measures of airway obstruction may also be generated (sRAW)
Gas diffusion techniques is also be used to measure static lung volumes but are also used to determine the efficiency of gaseous exchange.

Indications for Pulmonary function testing in children
Diagnosis
• Characterization of impairment in physiological function
• Quantification of impairment in physiological function
Monitoring of chronic disease
• Cystic Fibrosis
• Asthma
• Neuromuscular disease
Establishing the effectiveness of therapeutic intervention
• Asthma
• Cystic Fibrosis
Assessing risk of an intervention
• Anaesthetic
• Chemotherapy
• Fitness to fly

Lung Volumes and Capacities

Spirometry
Spirometry is the cornerstone of lung function. It uses forced ventilatory manoeuvres to assess maximal flow rates and dynamic lung volumes.
As the patient performs forced inspiratory and expiratory manoeuvres through the mouthpiece of the spirometer, a pneumotachometer inside the device measures pressure change across a fixed resistance, and these measurements can be used to calculate flow rates.
Older spirometers plot volumes against time. Newer spirometers plot flow-volume-loops and these are discussed here.

The flow-volume loop

The flow-volume loop plots inspiratory and expiratory flow rates against lung volume for maximal forced expiratory and inspiratory manoeuvres.

The forced inspiratory manoeuvre
• The forced inspiratory manoeuvre starts from a point of maximal expiration. The lung at this point is at residual volume (RV) As forcrd inspiration commences, lung volumes are low, airway patency is poor and so flow rates start slowly and increase as airway calibre increases. As inspiration progresses, inspiratory muscle strength tails off and flow rates again slow until total lung capacity (TLC) is achieved. Maximum flow rates are therefore seen around mid-inspiration giving the inspiratory limb of the flow-volume loop a domed appearance.

The forced expiratory manoeuvre
• To keep the lungs at TLC, a negative pleural pressure is maintained by contraction of the inspiratory muscles. Supportive structures of the lung transmit this negative pressure to the airways which are therefore held maximally patent and supported.
• On expiration, as lung volume decreases, airway support decreases and the airway becomes progressively more susceptible to narrowing or closure. This volume-dependant property of the airway is called dynamic compliance and airway narrowing as a consequence is termed dynamic compression.
• Dynamic compression does not occur during quiet expiration in the normal lung but becomes particularly important in a forced expiratory manoeuvre.
• During forced expiration, a large positive pleural pressure is applied to intrathoracic structures by contraction of expiratory muscles.
• Dynamic compression of the airway is at its minimum at TLC and consequently flow rates are at their highest. The peak expiratory flow rate (PEFR) is therefore seen at the beginning of forced expiration.
• As lung volume decreases through forced expiration, maximal flow rates also decrease because of increasing dynamic compression of the airway. In fact, as lung volumes fall, a dynamic compression-wave occurs along the airway, starting in the proximal airway and extending towards the bronchial periphery.
• Dynamic compression of the airway rather than effort actually limits the maximum expiratory flow rate that can be achieved during forced expiration. Flow rates therefore become effort-independent and can be taken as a true measure of airflow resistance. This phenomenon is the great advantage of using the forced expiratory manoeuvre.
• It is important to note that because children below the age of 5-7 years are generally unable to perform a forced expiratory manoeuvre where bronchial flow limitation is achieved, the direct relationship between measured flow rates and airflow resistance is lost, and so interpretation of spirometry in this age group may be difficult.
• The pattern and degree of dynamic compression (and therefore airflow resistance) seen on forced expiration will depend on intrinsic properties of the airway, including the stability of the bronchial walls, the degree of airway inflammation, airway wall thickness and smooth muscle tone. The forced expiratory manoeuvre is therefore invaluable in the assessment of obstructive airways disease.
• In patients with healthy lungs there is a predictable linear reduction in maximal flow rate as lung volumes decrease.
• In patients with obstructive small airways disease, flow rates fall quicker than anticipated as the lungs deflate, and the expiratory limb of the flow-volume loop appears “scooped out”.
• The affect of fixed large airways obstruction on flow dynamics can also be seen clearly o the flow-volume loop. The peak expiratory flow rate achievable will be limited by the fixed airways obstruction and this will produce a plateau to the expiratory limb of the flow-volume loop. As lung volumes continue to decrease during the expiration, maximal flow rates will eventually decrease to beneath the threshold defined by the obstruction, and at this stage the flow-volume loop assumes its normal dynamic. The same clipped appearance is seen in the inspiratory limb giving the classic square box appearance to the flow-volume loop.
• Mobile lesions causing upper airways obstruction may be more prominent in either inspiration or expiration. Mobile extrathoracic obstructions, e.g. vocal cord paralysis, have a more prominent effect during inspiration, and classically result in a square inspiratory limb and a normal expiratory limb on the flow-volume curve. Mobile intrathoracic large airway obstructions (e.g. a bulky mobile granuloma) may have a more prominent effect during expiration when the thorax is compressed, and may show a square expiratory limb and a normal inspiratory limb.
• The end of the forced expiratory manoeuvre in young healthy lungs occurs when expiratory muscles can contract no further. In diseased or older lungs, dynamic compression of small distal airways at the end of expiration may actually completely close the airways and further deflation becomes impossible. The remaining lung volume at the end of forced expiration is called the residual volume (RV) and is formally measures using plethysmography.This may be elevated in obstructive small airways disease.

Measurements in spirometry
• The central measurements taken from a forced expiratory manoeuvre are the forced vital capacity (FVC) and the forced expiratory volume in one second (FEV1). Normative data from cross-sectional studies are available for children. These values are age, height and weight dependant, but the most highly correlated parameter is height.
• FVC is reduced in restrictive lung defects. This may be due to poorly compliant lungs e.g. interstitial lung disease, to pulmonary hypoplasia, to respiratory muscle weakness, or to structural abnormalities of the thoracic cage. Children with muscle weakness e.g. Duchenne’s muscular dystrophy, will generally be unable to achieve bronchial flow limitation in forced expiration but should be able to perform a slow vital capacity (VC) manoeuvre which can be used to assess the degree of ventilatory restriction.
• FEV1 is reduced in obstructive small airways disease and is seen with scooping of the expiratory flow-volume loop. The degree of scooping is usually expressed as the ratio FEV1/VC % or FEV1/FVC %. Although FVC may also be reduced in more severe obstructive airways disease where full expiration is limited by closure of small airways, FEV1 will be more affected and so the ratio will always be reduced. The normal range for the ratio FEV1/FVC % is greater than 80%.
• FEF25-75 is defined as the average forced expiratory flow rate between 25%-75% lung capacity. A reduction in this parameter may be a more sensitive index of obstructive small airways disease than FEV1/FVC % as it reflects flow rates once the dynamic compression-wave has reached the small diseased airways.

Application of spirometry
• The forced expiratory manoeuvre requires inspiration to total lung capacity followed by a maximal hard and fast forced expiration which continues to residual volume. Children as young as 5 years of age may be able to perform useful spirometry and peak flow measurements if given a child friendly environment, good training and incentives.
• Older school children and adolescents may be able to perform satisfactory flow-volume loops with instruction alone, but breath-activated visual animated incentives, available on most electronic spirometers should definitely be used in the younger age group. A nose clip should be used where possible but this may prove difficult in younger children. The technician must always give encouragment throughout the test.
• Performance in younger children will improve as they become familiar with the process, and so children with chronic lung diseases should be introduced to the spirometer at an early age.
• Flow volume loops should be analysed in detail. Blows which are taken before total lung capacity is achieved, where maximal effort is not given, or where the child coughs or ends short of residual volume should be rejected. Several maximal blows should be performed before the test is complete
• Assessment for reversibility using bronchodilator therapy should be performed if the history or flow-volume loop is suggestive of obstructive airways disease. 5 puffs of salbutamol via spacer may be given in clinic, with repeat testing 10 minutes after administration. An increase in FEV1 of greater than 10%, with a supportive history and flow-volume dynamic, is highly suggestive of reversible airways disease.

Plethysmography
• Plethysmography is used to measure static lung volumes, in particular, functional residual capacity (FRC), total lung capacity (TLC) and residual volume (RV). Effort independent measures of airway obstruction may also be generated (sRAW, sGAW).
Measurement of Static lung volumes (TLC, RV)
• Calculations from plethysmography are based on Boyle’s law, which states that for a given mass of gas, the gas pressure x gas volume is a constant (at fixed temperature). Therefore changes in pressure measured during the procedure may be used to calculate lung volumes.
• The patient is sat in the sealed box and asked to breath normally through a mouthpiece, breathing air from outside the box. The patient is initially asked to sit in the box and breathe normally with a nose clip on. It takes about a minute for box temperature to stabilise. At the start of the test inspiration, an external occlusion is created by a shutter in the mouthpiece. Although flow is occluded, there is still chest expansion as thoracic gas is rarefied.
• Since the box is sealed, the air around the patient will be compressed slightly during this inspiratory manoeuvre and there will be a reduction in air volume in the box that is equal to the increase in thoracic gas volume (dV). This volume can be calculated using Boyle’s law using the pressure change observed in the box.
• During the same inspiration, pressure changes within the lung are also measured using the pressure transducer in the mouthpiece. Volume at the start of inspiration during tidal breathing is the functional residual capacity (FRC) of the lung, and this can be calculated again using Boyle’s law, using the pre- and post-inspiration airway pressures and the change in lung volume (dV) as measured using the external box measurements outlined above.
• FRC using this technique measures all the gas in the lung, including any that is trapped, as well as any gas in the stomach. It is therefore a measure of thoracic gas volume and should be referred to as FRCtgv.
• Once FRCtgv is known as an absolute quantity, full inspiration and full expiration with the shutter released can be used to define absolute values for total lung capacity (TLC) and residual volume (RV) respectively. Realistically these final manoeuvres are only possible in compliant children over the age of 6 years.

Measurement of airways resistance
sRAW and sGAW
• Plethysmography may also be used to measure airways resistance and is particularly useful in younger children who cannot perform a reliable forced expiratory manoeuvre for spirometry. Measurements are made during normal tidal breathing, requiring only passive cooperation from the child.
• Inspiration and expiration occur through generation of negative and positive alveolar pressure respectively. If this occurs against complete resistance (as described above) there is rarefaction and compression of intrathoracic gas respectively. In contrast, in a system of no resistance, flow will occur across the pressure difference between alveolus and mouth instantaneously and there will be no rarefaction or compression of intrathoracic gas. Change in lung volume here is in complete phase with observed flow, and this situation approximates to the normal lung.
• In the lung with high airways resistance, the volume to flow relationship becomes out of phase with a delay seen between the change in lung volume and the corresponding change in flow. In other words, intrathoracic gas becomes slightly rarified in inspiration and slightly compressed in expiration.
• To measure airways resistance using plethysmography, a pneumotachometer in the mouthpiece is used to measure flow rates during tidal breathing, while lung volume changes are simultaneously calculated using changes in box pressures as described above. By plotting volume change against flow, an s-shaped resistance loop can be generated. The long axis of the resistance loop is close to vertical in normal airways, and deviates towards the horizontal with increased airways resistance. This deviation is quantified as the parameter sRAW, the specific airways resistance. sGAW, (airway conductance) and is the reciprocal of sRAW.

The interrupter technique (RINT)
• Airways resistance may also be measured using the interrupter technique. This may be performed using standard plethysmograph equipment, although actual box pressure measurements are not used (portable systems also exist). Central to this technique is the indirect measurement of alveolar pressure during transient occlusion of the airway at the mouth. This relies on the assumption that alveolar pressure equilibrates with mouth pressure during airway occlusion so that measurements taken using a pressure transducer in the airway mask genuinely represent alveolar pressure. Airflow is measured at the mouth using the pneumotachometer just prior to occlusion, and inferences regarding airway resistance can be inferred from the pressure-flow relationship observed.
• Optimal timing of the occlusion within the breathing cycle remains unresolved. How best to measure the pressure from the post-occlusion oscillatory wave also remains contentious.
• RINT measurements have proven difficult to standardise although reference data has been published for healthy children. Some centres have incorporated RINT measurements into routine lung function procedure, but a role in the clinical setting remains limited.

Application of plethysmography
• Residual volume (RV) is raised in moderate to severe obstructive small airways disease. The RV/TLC % ratio generated using plethysmography is an important marker of disease progress in asthma and cystic fibrosis and should be documented regularly.
• Only passive co-operation is required for successful plethysmography and so generally speaking children of all ages can be tested, although apparautus may be different for different age groups. However, because the child needs to remain still during measurements, sedation is required for younger children and infants.
• In the younger age group, the need to use a nose clip, form a seal around the mouthpiece and prevent inflation of the cheeks during the manoeuvre makes repeatable acceptable results difficult to obtain. Using a face mask that covers the nose and mouth, with a built in flexible tube that keeps the mouth open and prevents nasal breathing improves results in this age group.
• In uncooperative children, tests may be attempted with an adult accompanying the child inside the box although technically this is more difficlut. If present in the box, the adult should prevent mouth bulging by stabilising the cheeks with his hands.
• In older fully compliant children, measurements may be made during panting rather than tidal breathing as this ensures that the vocal cords are open and do not contribute to measured airways resistance.
• sRAW measurements are highly repeatable
• sRAW and sGAW may help in the assessment of lung function in children as young as 2 years of age.
• Normative data exists for healthy school and pre-school children.
• Abnormal sRAW values are seen in pre-school children with Cystic Fibrosis and asthma. Cold air bronchial challenge (CACh) studied in 2-5 year old asthmatic children and healthy pre-school controls showed an increase in sRAW of >20% in 68% of asthmatics and only 7% of healthy controls. In a study of reversibility using beta-agonist therapy, a 25% decrease in sRAW provided good discrimination between pre-school asthmatic and healthy children.

Gas dilution techniques
Gas diffusion techniques can be used to measure static lung volumes and to determine the efficiency of gaseous exchange.

Multiple-breath closed circuit helium dilution
• This technique is based on dilution of helium in a rebreathing closed circuit.
• The volume of the circuit is known, the initial helium concentration in the circuit is measured and the amount of helium in the system calculated.
• The closed circuit is connected to a spirometer and mouthpiece via a 3-way tap. The patient breathes through the mouthpiece with a nose-clip on and tight seal around the mouth, with the 3-way tap initially connected to room air. Tidal volume is observed from the spirometer readings.
• At the start of the procedure, the patient is connected to the closed circuit at the end of a tidal expiration (FRC), and breathes through the circuit until helium is equally distributed through circuit and lungs. This point is marked by a levelling off of helium concentration in the system at a new lower level. This may take up to 10 minutes. Because helium is water insoluble and will not diffuse into the blood during the procedure, the total amount of helium in the system remains constant and so the new volume of distribution is simply calculated from the final helium concentration. CO2 is continuously absorbed by soda lime and oxygen continuously added so that the volume of the system remains constant.
• At the end of the procedure, the patient is asked to take a maximal inspiration and maximal expiration so that TLC and RV may also be derived. TLC derived using this technique is valled the alveolar volume VA.

Single-breath helium dilution
• Total lung capacity may also be calculated by comparing helium concentration provided in inspired air with that in expired air.
• The patient takes a single inspiration to total lung capacity and holds the breath for 10 seconds during which time approximate helium equilibration occurs throughout the lung. The volume of inspired gas and the helium concentration in inspired air is known, so VA can be calculated from the helium concentration in expired air.
• Pre-requisites for a successful test are the ability of the child to hold inspiration for 10 seconds, and a VC of 1.5 litres, as the first 750mls is discarded for washout of airways and apparatus dead space. Younger children will therefore find this test difficult. Children with severe restrictive lung disease and therefore a low VC will also be unable to perform this test successfully.
• Volumes measured using gas dilution techniques are generally marginally less than those measured using plethysmography. This discrepancy provides a measure of the degree of air trapping and is useful in the assessment of obstructive airways disease and particularly in CF.

Carbon Monoxide Transfer
TLCO and kCO are measures of gas diffusion capacity of the lung. Carbon Monoxide (CO) crosses the alveolar-capillary membrane and is taken up by red blood cells. If a gas mixture containing a known amount of CO is inhaled and held for 10-15 seconds and then exhaled, the difference in the amount of CO seen in inspired and expired air is the amount of CO that has diffused across the gaseous exchange surface of the lung. The total amount of CO transferred is called the Total Lung CO (TLCO). If the VA is measured at the same time using single-breath helium dilution, then the TLCO/VA can be used to generate a measure of gas transfer per unit lung volume, called the transfer factor or kCO.
kCO may be reduced
• Chronic Interstitial lung disease e.g. adenoviral bronchiolitis obliterans aspiration lung disease, extrinsic allergic alveolitis, pulmonary vasculitis syndromes.
• Interstitial fibrosis post-chemotherapy and radiation therapy.
• Pulmonary hypoplasia e.g. secondary to congential diaphragmatic hernia?? CORRECT
kCO may be increased
• Alveolar haemorrhage, since airspace red blood cells take up CO rapidly. e.g. primary pulmonary haemosiderosis, Goodpasture’s syndrome, Wegener’s disease, CF related haemoptysis.
• Restrictive lung disease from neuromuscular disease or deformed chest disease. These patients have essentially normal lungs that are poorly expanded. They may therefore have proportionally more gaseous exchange surface area per unit volume. This can be normalised by calculating predicted kCO using actual TLC rather than TLC predicted for height.
KCO may be normal
• Chronic obstructive airways disease and CF. In CF, ventilation-perfusion matching is good, bronchiectasis causes an increased bronchial circulation and pulmonary blood flow may be augmented by increased pressure swings due to dyspnoea.

Application of gas dilution techniques
• The older school age child should be able to perform single breath helium dilution techniques and measurements for transfer factor.
• In younger children, or those with a severe restrictive defect, multiple breath methods where the child inhales a mix of CO and helium while tidal breathing for several minutes can be used as an alternative. As kCO measurements using this technique are measured at FRC plus half tidal volume, as opposed to TLC for the single breath measurement, results using the two approaches are not directly comparable.
• Normative data for kCO levels in children exists for both single breath and rebreathing methods. In both cases these values correlate well with VA and height.
• Children with decreased alveolar diffusing capacity, who cannot be formally tested, will demonstrate desaturation on exercise as pulmonary blood supply exceeds alveolar diffusing capacity. This test is often called the poor man’s kCO.

Lung function test findings in restrictive lung disease
• Restrictive lung disease is defined as a total lung capacity below 80% predicted using plethysmography or gas dilution techniques. This remains the gold standard.
• A reduction in VC below 80% predicted seen on spirometry may also be used to define restriction. FEV1/FVC % ratio is classically elevated in restrictive lung disease
• FVC may also be reduced in obstructive lung disease or after a short expiration. If there is any doubt, static lung volujmes should be measured formally.
• FVC is effort dependant and may not be possible in children with muscle weakness. A slow VC in these situations is used to monitor disease progress
• A homogeneous drop in VC, RV and TLC is seen in parenchymal restrictive lung disease such as that seen with interstitial lung disease, hypoplasia or post-resection. In restriction from a hypodynamic state such as that seen in early neuromuscular disease, VC is reduced, RV may be increased, and TLC may be normal.
• The inspiratory capacity (IC), the volume from FRC to TLC, needs to be 15mls/kg to maintain adequate spontaneous ventilation. As post-operative pain may reduce IC by 50%, a value of less than 30mls/kg is commonly used as an indicator of patients who may require prolonged post-op ventilation.

Lung function test findings in obstructive airways disease
• Spirometry is the central tool for defining obstructive airways disease. Children from 5 years of age may be able to peform reliable spirometry.
• A reduced FEV1, FEF25-75 and FEV1/FVC% ratio, with a scooped expiratory limb of the flow-volume loop all suggest obstructive small airways disease. A clipped flow-volume loop suggests upper airway obstruction.
• Plethysmography or gas dilution techniques may reveal an increased RV and RV/TLC % ratio in moderate to severe obstructive small airways disease. RV can generally only be measured in compliant children above the age of 5 years.
• In pre-school children, the airways resistance measures sRAW and sGAW, obtained from plethysmography may be useful when a forced expiratory manoeuvre is unsuccessful.
• In infants and pre-school children, RINT and measures of airways resistance obtained through impedence techniques are being clarified but have limited clinical application at present.
• If an abnormality consistent with obstructive small airways disease is observed, improvement may be seen with bronchodilators and should be attempted.
• Bronchial hyperresponsiveness may be seen after direct bronchial challenge (histamine or methacholine), or indirect challenge (exercise or cold air), and is a useful tool if asthma is suspected despite normal lung function testing. In direct bronchila challenge with methacholine or histamine, increasing doses are nebulised between which spirometry is performed. The PC20 is defined as the provocative concentration that results in a 20% fall in FEV1. A PC20 of less than 1mg/ml indicates moderate to severe bronchial hyper-responsiveness, suggestive of asthma.

Infant lung function testing
• Most lung function tests that are available have been modified for use in infants. However, infant lung function testing is still prinicipally a research tool with little application in the clinical setting.
• Infants need to be sedated.
• Tests are labour intensive, technically demanding and time consuming.
• The majority of infants with respiratory disease have obstructive small airways disease, either from viral induced transient wheeze or from persistent wheeze. Other important groups include infants with chronic lung disease, tracheobronchomalcia and cystic fibrosis. Monitoring of drug responses and timing of interventions with disease progression is relevant to all these conditions
• Obstructive airways disease can be assessed in this age group using several methods. A forced expiratory manoeuvre for spirometry can be simulated using the rapid thoracic compression technique where bronchial flow limitation is achieved by rapid almost instantaneous inflation of a jacket wrapped around the infant’s chest.
• sRAW from body plethysmography is also a useful markers of airways resistance in this age group
• Multi-breath gas diffusion techniques may be used in unsedated infants. Ventilation inhomogeneity is seen in patients with obstructive airways disease and can be assessed if breath-by breath measurements of gas composition in expired air are recorded. Washout dynamics are generally delayed if ventilation is inhomogeneous.